Reacción #46630

Ecuación de reacción

(S)-tert-butyl 2-(5-(4-iodophenyl)-1,3,4-oxadiazol-2-yl)pyrrolidine-1-carboxylate

bis(pinacolato)diboron

KOAc

boronic acid

→

(S)-4-(5-(1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-1,3,4-oxadiazol-2-yl)phenylboronic acid

Rendimiento 22.0%

Disolventes

dioxane

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrowas degassed with a stream of Ar for 15 minutes
2. 2
   Temperaturacooled to room temperature
3. 3
   workup.ADDITIONpoured into ethyl acetate/H2O
4. 4
   OtroThe layers were separated
5. 5
   Extracciónthe aqueous phase was re-extracted with ethyl acetate (2×)
6. 6
   Lavadothe combined organic layers were washed (H2O, brine)
7. 7
   Secadodried (Na2SO4)
8. 8
   Filtraciónfiltered
9. 9
   OtroThe solvent was removed in vacuo
10. 10
    Otrothe residue purified by flash chromatography (hexane:ethyl acetate, 1:1)
11. 11
    Otroto give
12. 12
    OtroThis mixture was repurified by prep HPLC (CH3CN:H2O:TFA)

Procedimiento

A mixture of (S)-tert-butyl 2-(5-(4-iodophenyl)-1,3,4-oxadiazol-2-yl)pyrrolidine-1-carboxylate (24) (0.574 g, 1.30 mmol), bis(pinacolato)diboron (0.665 g, 2.62 mmol), KOAc (0.641 g, 6.53 mmol) and Pd(PPh3)4 (0.076 g, 0.0658 mmol) in dioxane (5 mL) was degassed with a stream of Ar for 15 minutes. The mixture was then heated at 100° C. for 12 hours, cooled to room temperature and poured into ethyl acetate/H2O. The layers were separated, the aqueous phase was re-extracted with ethyl acetate (2×) and the combined organic layers were washed (H2O, brine) and dried (Na2SO4) and filtered. The solvent was removed in vacuo and the residue purified by flash chromatography (hexane:ethyl acetate, 1:1) to give a mixture of the title boronate ester (25) and boronic acid (26). This mixture was repurified by prep HPLC (CH3CN:H2O:TFA) to afford (S)-4-(5-(1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-1,3,4-oxadiazol-2-yl)phenylboronic acid 26 as a colorless solid (0.101 g, 22%). 1HNMR (400 MHz, DMSO-d6) δ 8.31 (s, br, 2H), 7.94-8.00 (m, 4H), 5.03-5.10 (m, 1H), 3.37-3.42 (m, 2H), 2.31-2.40 (m, 1H), 1.92-2.04 (m, 3H). 1.38 (s, 3H), 1.18 (s, 6H); LCMS: Anal. Calcd. for C17H22BN3O5: 359. found: 360 (M+H)+.

Fuente